a study of ch-4051 in patients with rheumatoid arthritis (ra)

Conditions: Rheumatoid Arthritis

Summary: the purpose of this study is to determine if ch-4051 is a safe and effective treatment for rheumatoid arthritis.

multi-center, multi-national, double-blind, randomized, active-controlled (mtx), 3-month study with 4 doses of ch-4051 (0.3 mg, 1.0 mg, 3.0 mg and 3.0 mg with 1mg of folic acid supplementation p.o. daily) compared to a "standard" dose of mtx at 20 mg per week with 1 mg of folic acid supplementation p.o. daily. this study will be conducted in two parts: part a: patients will be randomized to 0.3 mg ch-4051, 1.0 mg ch-4051 or mtx. part b: patients will not be randomized into part b until the data monitoring committee has reviewed safety data from the part a when approximately 25 patients (10 patients in each ch-4051 dose groups and 5 patients in the mtx groups) have completed 3 months of treatment. at this time the dmc will make a recommendation whether or not to commence randomization to 3.0 mg ch-4051, 3.0 mg ch-4051 with 1.0 mg of folic acid.

Eligibility criteria:
inclusion criteria: * patients must be between the ages of 18 and 80; * have diagnosed active rheumatoid arthritis according to acr criteria functional class i-iii; * have at least 6 swollen joints (max = 66) and 6 tender joints (max = 68) at screening and baseline visits; * patients must have at least one of the following: * c-reactive protein \> 1.0 mg/dl at screening; * erythrocyte sedimentation rate \> 28 mm/hr; * patients must have been taking methotrexate between 15 and 25 mg/week for at least 3 months and at a stable dose for at least 6 weeks; * patients must be either rheumatoid factor (rf) or anti-cyclic citrullinated peptide (anti-ccp) positive; * patients must have voluntarily signed the informed consent. exclusion criteria: * patients who received previous therapy with any biologic agent; * patients currently taking any disease modifying anti-rheumatic drug (dmard) other than mtx; * previous non-biologic dmard therapy is permitted as long as their last dose was at least 30 days prior to baseline; * female patients of child bearing potential who are pregnant or who are not using two methods of contraception (at least one barrier: i.e. condom) with their partner; * male patients who are sexually active and not using two methods of contraception (at least one barrier: i.e. condom) with their partner; * patients with any current active infection or infections requiring iv drug therapy within 30 days of baseline or oral therapy within 15 days of baseline; * patients that have had any surgical procedures within 30 days of baseline; * patients with a history of hiv; * patients with hepatitis b surface antigen positive and/or hepatitis c antibody positive; * patients who consume more than 4 units of alcohol per week (1 unit = 5 ounces/150 ml of wine = 1.5 ounces/45 ml spirits = 12 ounces/360 ml of beer); * patients currently receiving any investigational drug or have received an investigational drug within 30 days of baseline or 5 half-lives of the investigational drug (whichever is longer); * patients with a history of cancer within the past 5 years other than a successfully treated, non-metastatic cutaneous squamous cell or basal cell carcinoma or cervical cancer in situ; * patients with a history of, or any, disease associated with an inflammatory arthritis other than ra; * patients with pulmonary fibrosis (chest x-ray must be taken within 28 days of screening); * patients receiving probenecid; * patients who have received any steroid injections within 30 days of baseline; * patients with concomitant diseases that are unstable (i.e. cardiac, pulmonary) or that may affect drug activity (i.e. absorption, reactions, change in kinetics); * patients, in the investigator's opinion, that have any significant renal or hepatic impairment; * patients with a serum creatinine level \> 1.5 mg/dl at screening; * patients with an alt \>1.5 uln at screening; * patients considered by the investigator to be an unsuitable candidate to receive ch-4051; * wheelchair or bed-bound patients.

Keywords: rheumatoid arthritis mtx ch-405 antifolates